What does Genesis 25:21 mean?
ESV: And Isaac prayed to the Lord for his wife, because she was barren. And the Lord granted his prayer, and Rebekah his wife conceived.
NIV: Isaac prayed to the Lord on behalf of his wife, because she was childless. The Lord answered his prayer, and his wife Rebekah became pregnant.
NASB: Isaac prayed to the Lord on behalf of his wife, because she was unable to have children; and the Lord answered him, and his wife Rebekah conceived.
CSB: Isaac prayed to the Lord on behalf of his wife because she was childless. The Lord was receptive to his prayer, and his wife Rebekah conceived.
NLT: Isaac pleaded with the Lord on behalf of his wife, because she was unable to have children. The Lord answered Isaac’s prayer, and Rebekah became pregnant with twins.
KJV: And Isaac entreated the Lord for his wife, because she was barren: and the Lord was entreated of him, and Rebekah his wife conceived.
NKJV: Now Isaac pleaded with the Lord for his wife, because she was barren; and the Lord granted his plea, and Rebekah his wife conceived.
Verse Commentary:
Once again, both barrenness and God's intervention play a role in the birth of the next generation in the line of God's people. Rebekah remained barren for a time, unable to have children. Isaac's mother, Sarah, remained childless until she was 90 (Genesis 17:17; 21:1–2). We're not told how much time passed between Isaac's prayer and Rebekah's pregnancy, but we do learn that Isaac was 60 when his sons are eventually born. That means the couple remained childless for 20 years.

The important thing to note is that Isaac took action. Prayer is action. He prayed to the Lord for his wife. God responded to Isaac's prayer. God had promised that multitudes would come from Abraham, but each birth in the line of God's chosen people thus far seems to have required special intervention from God Himself to take place. God's people understood that their children were gifts from Him.
Verse Context:
Genesis 25:19–28 describes the birth of Isaac and Rebekah's twin boys. After marrying when Isaac is 40, Rebekah does not become pregnant for 20 years, and only in response to Isaac's prayer to the Lord. Her pregnancy is so difficult that she approaches the Lord to ask why. His response is a prophecy about the divided nations that will come from her. That makes more sense when two children are born, one red and hairy, the other grabbing his brother's heel. The first is named Esau, who becomes a hunter loved by his father. The second is Jacob, a quiet, stay-at-home man favored by his mother.
Chapter Summary:
Genesis 25 is packed with information. Abraham marries another wife, most likely before Sarah died, and has six sons with her. Abraham dies at the age of 175 and is buried by both Isaac and Ishmael at the family-owned cave where Sarah was buried. Ishmael's 12 sons are listed, along with the region their tribes settled in, to the east of what would later become Israel. And, finally, God grants Isaac's prayer for Rebekah to become pregnant by giving the couple twins: the feuding Jacob and Esau.
Chapter Context:
The previous chapter tells the story of how Abraham's servant found a wife for Isaac from among Abraham's people. This chapter rushes to fill in the details of the end of Abraham's life before beginning the story of Isaac's years as patriarch. Abraham marries another woman and has six sons with her, eventually sending them all away from Isaac. Abraham dies and is buried with Sarah. Ishmael's 12 sons are listed, and then his death is recorded, as well. Finally, Isaac's twin boys are born in response to his prayer to the Lord.
Book Summary:
The book of Genesis establishes fundamental truths about God. Among these are His role as the Creator, His holiness, His hatred of sin, His love for mankind, and His willingness to provide for our redemption. We learn not only where mankind has come from, but why the world is in its present form. The book also presents the establishment of Israel, God's chosen people. Many of the principles given in other parts of Scripture depend on the basic ideas presented here in the book of Genesis. Within the framework of the Bible, Genesis explains the bare-bones history of the universe leading up to the captivity of Israel in Egypt, setting the stage for the book of Exodus.
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