This chapter introduces the concepts and methods associated with the scientific and evidence-based foundations of clinical assessment. Clinical assessment strategies are one common application of psychological assessment and are most beneficial to clients when they provide measures that are precise, sensitive to change, minimally inferential, well-validated for a particular assessment purpose and client, have well-documented sources of true and error variance, and are appropriately interpreted by the clinician. The scientific foundations of clinical assessment address the nature of behavior problems and of the causal variables that affect them, treatment research, the study of the psychometric characteristics of measures, the clinical judgments that are derived from the clinical assessment process, and errors in the clinical assessment process. To be most beneficial to clients, clinical assessment strategies and resulting measures must be valid indicators of the state of a variable when measured, sensitive indicators of change in a variable, valid and relevant for detecting important functional relations for a client’s behavior problems or treatment goals, and psychometrically sound for the client’s social and cultural contexts (such as the client’s age, ethnicity, and gender). The chapter ends with recommendations for conducting science-based clinical assessment.