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The incidence of invasive sino-pulmonary diseases due to non-<i>Aspergillus</i> hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: <i>Fusarium</i> spp., <i>Scedosporium</i> spp., <i>Lomentospora prolificans</i>, <i>Scopulariopsis</i> spp., <i>Trichoderma</i> spp., <i>Acremonium</i> spp., <i>Paecilomyces variotii</i>, <i>Purpureocillium lilacinum</i>, <i>Rasamsonia argillacea</i> species complex, <i>Arthrographis kalrae</i>, and <i>Penicillium</i> species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.