Calcium (Ca(2+)) is essential in regulating a plethora of cellular functions that includes cell proliferation and differentiation, axonal guidance and cell migration, neuro/enzyme secretion and exocytosis, development/maintenance of neural circuits, cell death and many more. Since Ca(2+) regulates so many fundamental processes, it could be anticipated that numerous Ca(2+) channels and transporters will assist in regulating Ca(2+) entry across the plasma membrane. Towards this several Ca(2+) channels such as voltage-gated channels, store-operated Ca(2+) entry (SOCE) channels, NMDA, AMPA and other ligand gated channels have been identified. In recent years research focus has been targeted towards identification of the precise function of these essential channels. Furthermore, characterization of these individual Ca(2+) channels has also gained much attention, since specific Ca(2+) channels have been shown to influence a particular cellular response. Moreover, perturbations in these Ca(2+) channels have also been implicated in a spectrum of pathological conditions. Hence, understanding the precise involvement of these Ca(2+) channels in disease conditions would presumably unveil avenues for plausible therapeutic interventions. We thus review the role of Ca(2+) signaling in select -disease conditions and also provide experimental evidence as how they can be characterized in a given cell.