Helicobacter pylori has been associated with colonization of gastro duodenal mucosa of humans from millions of years. The main burden of the disese is in the developing countries, due to overcrowding and poor hygiene. If left untreated it leads to lot of sequlae from minor to sinister diseases over a period of time. The main challenges that remain are prevention of H. pylori-related diseases by effective treatment and screening procedures and development of a vaccine, which can address all these issues including beneficial aspects of H. pylori. The literature pertaining to different aspects of H. pylori were scrutinized from Pubmed. Material on clinical behavior, complications of chronic gastric involvement, and prevention besides role of H. pylori in nongastric diseases and the latest trends of management was collected for research and review. We continue to face many challenges. The prevention of cancer of the stomach, a worst sequlae of H. pylori continues to be a big challenge despite population screening and prevention surveys being underway in many countries. On the other hand continued scientific work has now unfolded involvement of H. pylori in extragastric diseases like cerebrovascular, cardiovascular, idiopathic thrombocytopenia, sideroblastic anemia, mental diseases, and collagen vascular diseases. In contrast, the beneficial effects of H. pylori with respect to allergic diseases and obesity are now clear. Moreover, problem of drug resistance for eradication of H. pylori has arisen for which novel treatments are being tried. Lactobacillus reuteri having anti H. pylori action is emerging as one of the promising treatment.