Certain patient populations provide challenging clinical situations for the sedation provider. Patients with cardiovascular disease, chronic obstructive pulmonary disease (COPD), chronic renal failure, obesity, or advanced age are considered high risk and possess a higher rate of procedural complications. This chapter discusses important features of these higher-risk patients and practice management when sedation is required. COPD is frequently found in patients with chronic bronchitis or emphysema. Common procedural complications in this patient population include hypoventilation (hypoxemia and hypercapnia) and bronchospasm. Bronchospasm manifests as wheezing, and it is commonly caused by an exacerbation of the patient's COPD, but an anaphylactoid reaction to a sedation medication should be ruled out. Patients with known coronary artery disease (CAD) who become oversedated experience cardiac complications related to hypotension and/or hypoxemia. Medication used for sedation should be titrated in slowly, carefully watching hemodynamic response to the medication.