Human parasites cause several diseased conditions with high morbidity and mortality in a large section of population residing in various geographical areas. Nearly three billion people are suffering from either one or many parasitic infections globally with almost one million deaths annually. In spite of an extensive research and advancement in medical field, no effective vaccine is available against prominent human parasitic diseases that emphasize upon identification of novel targets for designing of specific inhibitors. Vitamin B6 is an important ubiquitous co-enzyme that participates in several biological processes and plays important role in scavenging ROS (reactive oxygen species) along with providing resistance to oxidative stress. Moreover, absence of the de novo vitamin B6 biosynthetic pathway in human parasites makes this pathway indispensable for the survival of these pathogens. Pyridoxal kinase (PdxK) is a crucial enzyme of vitamin B6 salvage pathway and participates in the process of vitamers B6 phosphorylation. Since the parasites are dependent on pyridoxal kinase for their survival and infectivity to the respective hosts, it is considered as a promising candidate for drug discovery. The detailed structural analysis of PdxK from disease causing parasites has provided insights into the catalytic mechanism of this enzyme as well as significant differences from their human counterpart. Simultaneously, structure based studies have identified the small lead molecules that can be exploited for drug discovery against protozoan parasites. Present review underscores structural and functional highlights of pyridoxal kinase for its implication to develop novel and potent therapeutics to combat fatal parasitic diseases.