The chapter examines the complex, multidimensional nature of treatment and medication nonadherence among individuals living with serious mental illness (SMI). It defines nonadherence as a dynamic behavioral phenomenon encompassing missed doses, refusal, and disengagement from therapeutic recommendations. Epidemiological data reveal high nonadherence rates across schizophrenia-spectrum, bipolar, and depressive disorders, with significant clinical, psychosocial, and economic consequences. Etiological factors include poor insight, neurocognitive deficits, substance use, stigma, and systemic barriers such as fragmented care and poor therapeutic alliances. The chapter emphasizes dimensional frameworks—biological, psychological, and behavioral—that interact to shape adherence behaviors. Behavioral strategies highlight motivational operations, self-regulation, and the impact of negative symptoms on engagement. The narrative underscores the need for integrated, culturally sensitive interventions targeting modifiable factors to improve adherence and outcomes. Through case illustration and empirical synthesis, the chapter advocates for personalized, dimensional approaches to understanding and addressing treatment nonadherence in SMI.