Clinical toxoplasmosis is a rare but often fatal disease that impacts several medical fields, including obstetrics, ophthalmology, transplantation, oncology and the context of the AIDS pandemic. The prognosis for patients with toxoplasmosis largely depends on timely treatment, which makes early diagnosis a priority for clinicians. However, diagnosing toxoplasmosis is a significant challenge due to the lack of specific clinical symptoms. This issue is further complicated by the high seroprevalence of Toxoplasma in the general population, which is far higher than the incidence of the disease. There are currently no clinically useful predictors for toxoplasmosis. Epidemiological studies and host–parasite interactions suggest that the incidence of toxoplasmosis depends on a combination of host and parasite factors. Significant risk factors include immunodeficiency, in utero exposure, genetic predisposition, anti-Toxoplasma antibody levels, older age, virulence of the strain, parasite burden and the infectious form of the parasite. Understanding these risk factors is important for clarifying the uncertainties regarding the incidence of toxoplasmosis and improving patient outcomes. In this review, we discuss the significance of these factors and current measurements for parasite-related factors. Additionally, we discuss potential preventive strategies that focus on screening as well as control of modifiable risk factors.