This chapter examines the critical sex and gender differences in psychosis, encompassing a broad spectrum of psychotic disorders. It highlights disparities in incidence, clinical presentation, and outcomes influenced by biological, hormonal, and psychosocial factors. Men typically experience earlier onset, higher rates of substance use, and more severe functional impairments, while women often present with later onset, better premorbid adjustment, and greater affective symptoms, potentially due to estrogen’s neuroprotective role. The chapter synthesizes evidence on neurodevelopmental pathways, trauma exposure, cognitive functioning, and treatment responses, underscoring the need for gender-sensitive diagnostic and therapeutic strategies. By addressing these differences, the chapter advocates for tailored interventions to optimize outcomes across the psychosis spectrum.