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This review focuses on the challenges and opportunities in the development of new forms of male-based contraceptives. Further these review concentrate on those recent advances in science and technology that offer possible inroads for shifting the paradigm for male-based contraception. The development of an effective, reversible and safe male contraceptive has been the focus of research around the world for more than 30 years. There are numerous challenges in the development of a male contraceptive. Unlike women, who produce one functional gamete per month, men produce near about 100 million sperm every day. Based on animal studies and clinical results from treating hypogonadotropic hypogonadal men, a contraceptive agent that would functionally suppress either the formation or maturation of spermatozoa with a 90% efficacy would probably have little or no effect on fertility. Several non-hormonal avenues for male contraception are being developed, and a recent study provides an exciting novel approach to male contraception by administration of a drug that modifies the biosynthesis of glycosphingolipids.