Anthracnose is a severe disease caused by Colletotrichum spp. on several crop species. Fungal infections can occur both in the field and at the post-harvest stage causing severe lesions on fruits and economic losses. Physical treatments and synthetic fungicides have traditionally been the preferred means to control anthracnose adverse effects; however, the urgent need to decrease the use of toxic chemicals led to the investigation of innovative and sustainable protection techniques. Evidence for the efficacy of biological agents and vegetal derivates has been reported; however, their introduction into actual crop protection strategies requires the solutions of several critical issues. Biotechnology-based approaches have also been explored, revealing the opportunity to develop innovative and safe methods for anthracnose management through genome editing and RNA interference technologies. Nevertheless, besides the number of advantages related to their use, e.g., the putative absence of adverse effects due to their high specificity, a number of aspects remain to be clarified to enable their introduction into Integrated Pest Management (IPM) protocols against Colletotrichum spp. disease.