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This chapter provides a brief overview of how natural gradients (e.g., latitude, altitude, and landscape gradients) affect host–parasite interactions involving blood parasites in wildlife and how biotic and abiotic factors act as disruptors. These gradients have a direct impact on prevalence, parasitemia, and the observed relationships between parasites and hosts. In the tropical zone, altitudinal gradients imitate the behavior of the latitudinal gradient, since low temperatures are common at both higher altitudes and higher latitudes. Temperature is one of the determining factors of the diversity of vectors, hosts, and vegetation that affect parasite transmission cycles. Furthermore, within landscapes, there may be many types of elements producing gradients. For instance, increasing distance from water sources, anthropogenic degradation, and even sequential stages of succession and interspersion of vegetation communities would affect host–parasite–vector interactions. However, such effects do not always operate in the same direction because responses are context sensitive. We also discuss the importance of an integrative diagnosis, using microscopic and molecular approaches, which allow better approximations and analyses at the parasite species level, thus producing stronger conclusions. The same detail is recommended for studies on the hematophagous fauna of potential vectors. The life cycle of different parasite species has its own set of characteristics, and it corresponds to the researchers to unravel the puzzle and to avoid unwarranted generalizations.