Historically, pharmacotherapy for schizophrenia was mainly focused on finding drugs to treat psychotic symptoms only, without addressing other crucial domains of the disorder such as cognitive impairments. As a result, these domains have remained undertreated. In this review, we discuss recent preclinical research efforts, including investigation of synaptic mechanisms as well as intracellular signalling pathways and mechanisms involved in neuroplasticity and cell resilience, that may represent new mechanisms participating in the pathogenesis of schizophrenia, particularly at the level of the prefrontal cortex and hippocampus, and that might lead to the development of drugs that can counteract, at least partially, the cognitive impairments typical of schizophrenia.