<b><i>Background:</i></b> The burden of <i>Helicobacter pylori</i> infection (HPI) in Africa remains high with varying levels of prevalence among children and adults reported in different regions of the continent. Persistent and uneradicated HPI could result in gastric cancer, although less severe pathological outcomes have been reported among Africans – the so-called “African enigma.” <b><i>Summary:</i></b> Analysis of endoscopic findings of the upper gastrointestinal tract demonstrates similarities with that of patients from the West. Thus, it could be asserted that the true picture of HPI in Africa is yet to be unveiled due to several challenges including inadequate health-care system, lack of treatment guidelines and standardized protocol for diagnosis, and lack of data. This review explores the prevalence, diagnosis, treatment, and health-care system in Africa as it relates to HPI, thus providing an update and highlighting the need for an African HPI guideline. <b><i>Key Messages</i></b>: There is high prevalence of Helicobacter pylori infection (HPI) in Africa with an increasing burden of antibiotic resistance. Various methods including invasive and noninvasive methods are deployed in the diagnosis of HPI in Africa. There is a need for consensus on diagnosis and treatment of HPI in Africa.