The scabies mite, Sarcoptes scabiei var hominis, is an obligate ectoparasite of humans. It has been a source of distress for humanity since antiquity. The troublesome mite is emerging triumphant over current acaricidal agents with reports of emerging resistance and treatment failures. Scabies in endemic areas and crusted scabies offer additional management challenges. Exploration of indigenous plants and better understanding of mite biology and pathogenesis provide opportunities for the development of novel agents for this common pest. We review the recent diverse approaches to scabies, including the use of novel plant products with a better safety profile, translating the use of moxidectin from veterinary practice to human scabies, vaccination, immunotherapy, and development of drugs that directly target mite molecules.