The relationship between pharmacological treatment and structural and functional brain characteristics in the major psychoses is a matter of lively debate. In the case of schizophrenia, a better definition of the role played by antipsychotic treatment on the progressive trajectory of brain abnormalities is crucial to understand the nature of such abnormalities and whether they could be moderated or prevented. In this respect, contrasting data have emerged on the role of first-generation vs second-generation antipsychotics. From a clinical viewpoint, some evidence exists on the relationship between brain structural and functional changes and clinical response to antipsychotic medication. This may help to identify patients who will benefit from a given treatment, a possibility especially useful for costly treatments or treatments with complex management or serious side effect profiles. The goal of the current chapter is to review the existing evidence about the impact of antipsychotic drug treatment on brain structure, as assessed by structural magnetic resonance imaging (sMRI), and function, as assessed by functional neuroimaging techniques (i.e., PET, SPECT, fMRI, MRI spectroscopy) with a focus on prospective, longitudinal studies. Furthermore, change of positive and negative symptoms (both primary and secondary) under treatment with respect to brain structural, functional, and neurochemical correlates is discussed.