Invasive fungal and fungal-like infections contribute to substantial morbidity and mortality in immunocompromised individuals. The incidence of these infections is increasing—largely because of rising numbers of immunocompromised patients, including those with neutropenia, human immunodeficiency virus, chronic immunosuppression, indwelling prostheses, burns, and diabetes mellitus, and those taking broad-spectrum antibiotics. Invasive fungal pathogens include primary mycotic organisms such as Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, and Paracoccidioides brasiliensis, which are true pathogens and inherently virulent. Secondary mycotic organisms such as Candida and Aspergillus species, Cryptococcus neoformans, Pneumocystis jirovecii, and Mucorales fungi are opportunistic, less virulent pathogens. Nocardia and Actinomyces species are gram-positive bacteria that behave like fungi in terms of their growth pattern and cause fungal-like invasive indolent infections; thus, these organisms are included in this review. Fungal and fungal-like infections can affect a variety of organ systems and include conditions such as meningitis, sinusitis, osteomyelitis, and enteritis. As awareness of these infections increases, timely diagnosis and treatment will become even more important. Imaging has a critical role in the evaluation of disease activity, therapy response, and related complications. Using an organ-based approach with computed tomography, magnetic resonance imaging, and ultrasonography to gain familiarity with the appearances of these infections enables timely and accurate diagnoses.