Schiff based ligands and their complexes have emerged as potential drug candidates. Owing to their excellent chelating tendency, they easily coordinate with transition metals which have vacant orbitals. Transition metal complexes have several advantages because of their better acceptability and low toxicity in biological systems. These metals also serve as micronutrients and as co-factors of various metallo-enzymes which justifies the need of their designing and synthesis. Many modifications have been suggested in the ligand moiety for the purpose of activity enhancement and some of them have been described in the present review. These modifications have enhanced better potency against a number of diseases and resulting in low toxicity and better solubility in vivo. The transition metal complexes with Schiff based complexes have exhibited an array of activities including anticancer, antioxidant and antimicrobial. Their analytical applications have also been reported. The present review summarizes some of the recent advances in the field of synthesis and designing of new Schiff based complexes particularly with first transition series metals and their medicinal applications.