We provide in this manuscript a detailed and comprehensive overview of systemic therapy considerations for the following histologic tumor types of the larynx: verrucous carcinoma (VC), HPV-related SCC, basaloid SCC (BSCC), lymphoepithelial carcinoma (LEC), adenosquamous carcinoma (ASC), typical and atypical carcinoid, small cell neuroendocrine carcinoma (SCNC), large cell neuroendocrine carcinoma (LCNC), NUT midline carcinomas (NUTMC), melanoma, adenoid cystic carcinoma, rhabdomyosarcoma (RMS), malignant fibrous histiocytoma (MFH), lymphoma, mucoepidermoid carcinoma (MEC), acinic cell carcinoma, and spindle cell carcinoma (SpCC).