Perioperative pain management for obese patients is daily challenges for anesthesiologists especially if complex comorbidities such as Obstructive Sleep Apnea and cardiovascular disease coexist. Limitations to effective pain management in this group are multifactorial, that includes technical difficulty with regional techniques, limited expertise, unavailability of standardized guidelines and lack of familiarity with recent multimodal analgesic regimens. Opioid-related complications such as narcotic-induced ventilatory depression in these group of patients poses another critical concern for both trainees and the experienced anesthesiologists. This chapter is intended for residents, fellows, as well as senior perioperative physicians, and will explore various regional and pharmacological options for acute pain management in this special population based on recent advances and available evidence.