This chapter is devoted to the evidence of causes of disease. It focuses on the following: the concept of causes in medicine; judgmental and computational criteria of the cause–effect relationship; the two main types of etiological studies and the contribution of their computational products to causal inference. The chapter examines the most important clinical precautions required to avoid errors and bias in analytical research; etiological research of unplanned events, such as the investigation of disease outbreaks; and the challenges of multiple causes and multiple consequences. It discusses the implications of the results of etiological studies for practical decision-making in preventive medicine and clinical care. The chapter outlines some important principles in the search for causes in medicine: assessment of risks; study of contrasts; assessment of impact; and assessment of imputability of effect to a cause.