Although acromegaly has been associated with increased mortality rates, evidence shows that the application of the recent treatment modalities has reduced the risk of death in these patients, being comparable with the general population. As a result of the changing trends regarding mortality, the aim is to review the current literature to create enough evidence about the recent trends of mortality in patients with acromegaly. Moreover, this review aims to identify the possible etiology and the related risk factors. Old studies have reported that cardiovascular complications were the major etiology for death among acromegalic patients. However, recent studies showed that malignancies-induced complications might be the leading factor, while other studies reported that cardiovascular complications are still the main culprit. Nonetheless, the recently estimated risk is similar to that in the general population. Studies reported a decrease in mortality rates among patients with acromegaly within the last decades, which is probably attributable to the recent changes in the management updates, the less frequent exposure to radiotherapy and focus on the common cardiovascular disorders associated with the disease. This review also found that exposure to radiotherapy, old age, hypopituitarism, active acromegaly, and high growth hormone (GH) levels are significant predictors of mortality in acromegalic patients. In conclusion, more effort should be made to decrease GH to favorable levels based on the recent guidelines.