Background: Acute appendicitis is one of the most common surgical emergencies globally. Its incidence is increasing in low- and middle-Human Development Index countries (LMHDICs). Although a proportion of patients can be treated successfully with non-operative management consisting of antibiotics, supportive therapy, and close observation, current diagnostic algorithms lack the granularity to identify these patients accurately. Methods: We reviewed published literature describing practice patterns and clinical outcomes for appendicitis in LMHDICs and compared them with studies from high-Human Development Index countries, as well as guidelines published by international surgical societies. Results: We identified shortcomings in current diagnostic and therapeutic strategies used in LMHDICs. Delays in obtaining surgical care inherent in many LMHDIC healthcare systems make prompt surgical care the mainstay for the treatment of acute appendicitis. Laparoscopic appendectomy leads to better outcomes than open appendectomy in resource-constrained settings and when available should be the surgical technique of choice. Conclusions: Acute appendicitis is common in LMHDICs, and if possible, laparoscopic appendectomy should be the procedure of choice.