Fungi, algae, plants, protozoa, and bacteria are all known to form spores, especially hardy and ubiquitous propagation structures that are also often the infectious agents of diseases. Spores can survive for thousands of years, frozen in the permafrost (Kochkina et al., 2012), with the oldest viable spores extracted after 250 million years from salt crystals (Vreeland, Rosenzweig, & Powers, 2000). Their resistance to high levels of UV, desiccation, pressure, heat, and cold enables the survival of spores in the harshest conditions (Setlow, 2016). For example, Bacillus subtilis spores can survive and remain viable after experiencing conditions similar to those on Mars (Horneck et al., 2012). Spores are disseminated through environmental factors. Wind, water, or animal carriage allow spores to be spread ubiquitously throughout the environment. Spores will break dormancy and begin to germinate once exposed to favorable conditions. Germination is the mechanism that converts the spore from a dormant biological organism to one that grows vegetatively and is capable of either sexual or asexual reproduction. The process of germination has been well studied in plants, moss, bacteria, and many fungi (Hohe & Reski, 2005; Huang & Hull, 2017; Vesty et al., 2016). Unfortunately, information on the complex signaling involved in the regulation of germination, particularly in fungi remains lacking. This chapter will discuss germination of fungal spores covering our current understanding of the regulation, signaling, outcomes, and implications of germination of pathogenic fungal spores. Owing to the morphological similarities between the spore-hyphal and yeast-hyphal transition and their relevance for disease progression, relevant aspects of fungal dimorphism will be discussed alongside spore germination in this chapter.