In the present review article human diseases caused by various groups of pathogens have been explained with its etiology, epidemiology and treatment. In addition, effect of climatic changes on parasites and pathogens has been demarcated with rising incidences of diseases. In response to environmental changes, mainly external and internal microenvironment of body and drug regimens taken by patients; virus is regularly changing its form and new mutant variants are coming out. These are circulating in many Indian states and cross border countries and causing high infectivity and mortality in human patients. These variants with new mutations are challenging existing drugs and other prophylactic measures and massively disrupting functions of a tissue, organ, or entire organism. Diseases caused by viruses are showing new trends in virulence, with high infectivity, morbidity and mortality. Due to climatic effect and drug resistance and new mutations in pathogens disease burden has been exacerbated enormously at global level. In all cases of helminthes, protozoan’s, fungi, bacteria, virus pathogens and parasites available drug structure seem to be failed or their usefulness has been much reduced due to evolution of new mutant variants with multiple drug resistance. There are serious failures at the level of operation, management and control of disease. The utmost failure is due to lack of appropriate vaccine, drug regimens, clinical care and awareness among people. These are major reasons that is why diseases become uncontrolled and unmanageable.