In all animals, a key event in the transition from maternal control of development to control by products of the zygotic genome is the elimination of a significant fraction of the mRNAs loaded into the egg by the mother. Clearance of these maternal mRNAs is accomplished by two activities: the first is maternally encoded while the second requires zygotic transcription. Recent advances include identification of RNA-binding proteins that function as specificity factors to direct the maternal degradation machinery to its target mRNAs; small RNAs-most notably microRNAs-that function as components of the zygotically encoded activity; signaling pathways that trigger production and/or activation of the clearance mechanism in early embryos; and mechanisms for spatial control of transcript clearance.