Toxoplasma gondii and Neospora caninum are important causes of reproductive loss in ruminant species worldwide. Both parasites cause disease during pregnancy that may result in foetal death or birth of live congenitally infected offspring. T. gondii is also an important human pathogen with the main risk groups including pregnant women and immuno-compromised individuals, although clinical disease has also been observed in outbreaks among immuno-competent people. While the two parasites are closely related there are distinct differences between the two in their interactions with different host species and subsequent clinical outcome. This paper discusses the respective host-parasite relationships in ovine toxoplasmosis and bovine neosporosis and how the immune response may be host-protective, parasite-protective or contribute to disease pathogenesis, and how this knowledge may help in the development of more effective and targeted vaccination strategies.