Cognitive disorders and symptoms are key features of many mental and neurological diseases, with a large spectrum of impaired domains. Because of their possible evolution and detrimental functioning impact, they are a major pharmacological target for both symptomatic and disease-modifier drugs, while few cognitive enhancers have been marketed with an insufficient efficiency. It explains the need to model these cognitive disorders beyond the modelization of mental or neurological diseases themselves. According to the experimental strategy used to induce cognitive impairment, three categories of models have been identified: neurotransmission-driven models; pathophysiology-driven models; environment-driven models. These three categories of models reflect different levels of integration of endogenous and exogenous mechanisms underlying cognitive disorders in humans. Their comprehensive knowledge and illustration of their pharmacological modulation could help to propose a renewing strategy of drug development in central nervous system (CNS) field at a time when the academic and industrial invest seems to be declining despite the medical and social burden of brain diseases.