Ureases have emerged as significant virulence factors implicated in the pathogenesis of many clinical conditions such as pyelonephritis, hepatic coma, peptic ulceration, and the formation of injection-induced urinary stones and stomach cancer. They have also been identified as important targets in research both for human and animal health, as well as in agriculture. Strategies based on urease inhibition are the main treatment of diseases caused by urease-producing bacteria. So, in the present context, a diverse library of chemical structures is known to possess remarkable inhibitory activities against urease enzymes. The current review article summarizes and discusses endeavours towards the developments in the burgeoning field of urease inhibition in medicinal chemistry, with an emphasis on the insights that have been gleaned into the structural features that contribute to high and promising levels of anti-urease activity.