Laparoscopic sleeve gastrectomy (LSG) has consistently remained the most commonly performed bariatric procedure worldwide over the past decade, mainly due to sustained weight loss, significant improvement or remission of obesity-related complications, and dramatic restoration of quality of life. The lower technical demands required to perform the procedure, based on a single upper abdominal approach and the absence of gastrointestinal anastomosis, which generally demands shorter operative time, may be very advantageous in patients with compromised health status or with specific intestinal diseases. Furthermore, the absence of intestinal bypass may also be favorable in some situations of diseases unrelated to obesity that require the use of lifelong medications. The advantages of the sleeve have been widely demonstrated in the general population with obesity, but the choice of LSG in patients with special situations such as cirrhosis, inflammatory bowel disease, and in the setting of organ transplantation may be even more advisable.