Fungi are one of the most neglected pathogens apparent from the fact that the Amphotericin B, a polyene antibiotic, discovered way back in 1956 is still used as a gold standard for antifungal therapy. Past two decades have witnessed a dramatic rise in the incidences of life threatening systemic fungal infections. This can be ascribed to the increase in the number of immuno-compromised patients due to rise in HIV infected population, cancer chemotherapy and indiscriminate use of antibiotics. Majority of clinically used antifungals suffer from various drawbacks in terms of toxicity, efficacy and cost, and their frequent use has led to the emergence of resistant strains. Hence, there is a great demand for novel antifungals belonging to wide range of structural classes, selectively acting on novel targets with fewer side effects. This article aims at reviewing recent efforts made towards discovering novel antifungal drug targets and investigational molecules acting on them.