And Isaac entreated the LORD for his wife, because she was barren: and the LORD was entreated of him, and Rebekah his wife conceived.

Wesley's Notes

25:21 And Isaac intreated the Lord for his wife - Though God had promised to multiply his family, he prayed for it; for God's promises must not supersede but encourage our prayers, and be improved as the ground of our faith. Though he had prayed for this mercy many years, and it was not granted, yet he did not leave off praying for it.

Jamieson-Fausset-Brown Bible Commentary

21. Isaac entreated the Lord for his wife-Though tried in a similar way to his father, he did not follow the same crooked policy. Twenty years he continued unblessed with offspring, whose seed was to be "as the stars" [Ge 26:4]. But in answer to their mutual prayers (1Pe 3:7), Rebekah was divinely informed that she was to be the mother of twins, who should be the progenitors of two independent nations; that the descendants of the younger should be the more powerful and subdue those of the other (Ro 9:12; 2Ch 21:8).

Matthew Henry's Concise Commentary

25:19-26 Isaac seems not to have been much tried, but to have spent his days in quietness. Jacob and Esau were prayed for; their parents, after being long childless, obtained them by prayer. The fulfilment of God's promise is always sure, yet it is often slow. The faith of believers is tried, their patience exercised, and mercies long waited for are more welcome when they come. Isaac and Rebekah kept in view the promise of all nations being blessed in their posterity, therefore were not only desirous of children, but anxious concerning every thing which seemed to mark their future character. In all our doubts we should inquire of the Lord by prayer. In many of our conflicts with sin and temptation, we may adopt Rebekah's words, If it be so, why am I thus? If a child of God, why so careless or carnal? If not a child of God, why so afraid of, or so burdened with sin?