Salmonella, a genus of the family Enterobacteriaceae with over 2450 species, has been responsible for diseases ranging from non-typhoidal salmonellosis to typhoidal salmonellosis. Several groups of antibiotics such as β-lactams, aminoglycosides, tetracyclines, quinolones, cephalosporins and sulfonamides are used against Salmonella species. Many Salmonella species had developed resistance to several antibiotics over the years. Two major groups of mechanism of resistance demonstrated by this pathogen are (1) Biochemical Mechanisms; such as enzymatic inactivation, prevention of access to the target site by antibiotics and active efflux pumps. (2) Genetic mechanisms; such as mutation, horizontal gene transfer and vertical gene transfer. Some factors identified to contribute to the emergence and dissemination of antibiotic resistant-Salmonella include; miss-used of antibiotics, used of antibiotics in agriculture, unregulated sales of antibiotics, inappropriate prescription and dispensing practices, and poor hygiene practices (external or behavioural factors), the presence of mobile genetic elements in the organisms; plasmid DNA, transposons, integrons etc. The clinical and public health consequences, and the strategies to stem the growing tides associated with drugs resistance in Salmonella species are herein discussed. A more radical approach and commitment from the policy makers in health sector to solving problems emanating from increasing spread of resistant Salmonella is advocated.