This systematic review summarizes the current knowledge on Hepatozoon (Eucoccidiorida: Hepatozoidae) in wild mammals of the Americas. Hepatozoon is a genus of protozoan hemoparasites with heteroxenous life cycles, switching between vertebrates and blood-feeding invertebrates. The review highlights the lack of harmonized data on the epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity of Hepatozoon in the Americas. The review analyzed 1406 studies, identifying 84 that met the inclusion criteria. Data were collected from 11 out of 35 countries in the Americas, with Carnivora and Rodentia orders having the most characterizations. Bats, ungulates, and shrews were the least affected groups. The study identified several species of Hepatozoon, including H. americanum, H. canis, H. didelphydis, H. felis, H. milleri, H. griseisciuri, and H. procyonis. However, many genospecies remain to be formally described. The detection of Hepatozoon has primarily relied on conventional PCR, with the implementation of specific real-time PCR being recommended for improved diagnosis. The V4 region of the 18S rRNA gene has been widely sequenced for identification, but mitochondrial and apicoplast markers should also be targeted for more accurate species determination. Phylogenetic analysis of 18S rDNA sequences revealed two main clades: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The review emphasizes Hepatozoon as a potential disease agent in threatened wild mammals and the role of wild canids as spreaders of Hepatozoon infections in the Americas. The study also highlights the need for further research to understand the genetic diversity, transmission dynamics, and ecological roles of Hepatozoon in the Americas. The findings suggest that Hepatozoon has a wide host range and may be transmitted through various ecological interactions, including predation, shared ectoparasites, and vector-mediated transmission. The study underscores the importance of understanding Hepatozoon's role in ecosystem dynamics and wildlife conservation.This systematic review summarizes the current knowledge on Hepatozoon (Eucoccidiorida: Hepatozoidae) in wild mammals of the Americas. Hepatozoon is a genus of protozoan hemoparasites with heteroxenous life cycles, switching between vertebrates and blood-feeding invertebrates. The review highlights the lack of harmonized data on the epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity of Hepatozoon in the Americas. The review analyzed 1406 studies, identifying 84 that met the inclusion criteria. Data were collected from 11 out of 35 countries in the Americas, with Carnivora and Rodentia orders having the most characterizations. Bats, ungulates, and shrews were the least affected groups. The study identified several species of Hepatozoon, including H. americanum, H. canis, H. didelphydis, H. felis, H. milleri, H. griseisciuri, and H. procyonis. However, many genospecies remain to be formally described. The detection of Hepatozoon has primarily relied on conventional PCR, with the implementation of specific real-time PCR being recommended for improved diagnosis. The V4 region of the 18S rRNA gene has been widely sequenced for identification, but mitochondrial and apicoplast markers should also be targeted for more accurate species determination. Phylogenetic analysis of 18S rDNA sequences revealed two main clades: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The review emphasizes Hepatozoon as a potential disease agent in threatened wild mammals and the role of wild canids as spreaders of Hepatozoon infections in the Americas. The study also highlights the need for further research to understand the genetic diversity, transmission dynamics, and ecological roles of Hepatozoon in the Americas. The findings suggest that Hepatozoon has a wide host range and may be transmitted through various ecological interactions, including predation, shared ectoparasites, and vector-mediated transmission. The study underscores the importance of understanding Hepatozoon's role in ecosystem dynamics and wildlife conservation.