Practical relevance: Procedural sedation and analgesia (PSA) describes the process of depressing a patient’s conscious state to perform unpleasant, minimally invasive procedures, and is part of the daily routine in feline medicine. Maintaining cardiopulmonary stability is critical while peforming PSA. Clinical challenges: Decision-making with respect to drug choice and dosage regimen, taking into consideration the cat’s health status, behavior, any concomitant diseases and the need for analgesia, represents an everyday challenge in feline practice. While PSA is commonly perceived to be an uneventful procedure, complications may arise, especially when cats that were meant to be sedated are actually anesthetized. Aims: This clinical article reviews key aspects of PSA in cats while exploring the literature and discussing complications and risk factors. Recommendations are given for patient assessment and preparation, clinical monitoring and fasting protocols, and there is discussion of how PSA protocols may change blood results and diagnostic tests. An overview of, and rationale for, building a PSA protocol, and the advantages and disadvantages of different classes of sedatives and anesthetics, is presented in a clinical context. Finally, injectable drug protocols are reported, supported by an evidence-based approach and clinical experience.