Helicobacter pylori infection occurs worldwide. The common modalities used for the diagnosis are still rapid urease test (RUT) and histology in developing countries. Self-prescription is common as medications are freely available over-the-counter of pharmacies for sale without prescriptions. On proton pump inhibitors and histamine-2 receptor blockers (H2RB), diagnostic yield of both RUT and histology is reduced from antrum and corpus. The exclusive use of the rapid urease test for the diagnosis of Helicobacter pylori cannot be recommended in patients with prior PPI use. In these patients, polymerase chain reaction for H. pylori is more sensitive than RUT and histology.