Learning and memory are associated with the formation and modification of neuronal assemblies: populations of neurons that encode what has been learned and mediate memory retrieval upon recall. Functional studies of neuronal assemblies have progressed dramatically thanks to recent technological advances. Here we discuss how a focus on assembly formation and consolidation has provided a powerful conceptual framework to relate mechanistic studies of synaptic and circuit plasticity to behaviorally relevant aspects of learning and memory. Neurons are likely recruited to particular learning-related assemblies as a function of their relative excitabilities and synaptic activation, followed by selective strengthening of pre-existing synapses, formation of new connections and elimination of outcompeted synapses to ensure memory formation. Mechanistically, these processes involve linking transcription to circuit modification. They include the expression of immediate early genes and specific molecular and cellular events, supported by network-wide activities that are shaped and modulated by local inhibitory microcircuits.