The capacity of the brain to undergo plastic changes is conceived as a pre-requisite for learning and memory. Activity-dependent modifications of synaptic strength, coined synaptic plasticity represents one of the cellular mechanism that underlie this cognitive process. Obviously, factors that regulate neurotransmitter release, and that alter the localization and functions of neurotransmitter receptors play significant roles in modulating synaptic plasticity. In a different perspective, growing body of evidence has pointed to the role of cell adhesion molecules (CAMs) in modulating synaptic efficacy in an activity-dependent manner, presumably through the alteration of adhesive force between apposing pre- and post-synaptic membranes of synapses. Two CAM genetic mutant mice with restricted disruption of L1 or NCAM gene to their hippocampi at postnatal stage have been generated. Our findings showed that these mutants are impaired in spatial learning tasks, suggesting functional implications of these molecules in learning and memory. Combining mouse molecular genetics, cell biology, electrophysiology, and behavioural analyses, the molecular and cellular mechanisms upon which CAMs are involved in learning and memory will be further investigated. Understanding the cognitive functions of CAMs will not only address the intriguing question of how memory is encoded and consolidated, but also shed light on the etiology of neurological diseases like mental retardation.