ABSTRACT The worldwide prevalence of allergic diseases has drastically increased in the past decades. Recent studies underline the importance of microbial exposure for the development of a balanced immune system. Consequently, probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. However, clinical probiotic intervention studies have so far yielded conflicting results. There is increasing awareness about the importance of host-associated factors that determine whether an individual will respond to a specific probiotic treatment, and it is therefore crucial to promote a knowledge-based instead of an empirical selection of promising probiotic strains and their administration regimen. In this Review, we summarize the insights from animal model studies of allergic disease, which reveal how host-related factors – such as genetic makeup, sex, age and microbiological status – can impact the outcomes of preventive or curative probiotic treatment. We explore why and how these factors can influence the results of probiotic studies and negatively impact the reproducibility in animal experiments. These same factors might profoundly influence the outcomes of human clinical trials, and can potentially explain the conflicting results from probiotic intervention studies. Therefore, we also link these host-related factors to human probiotic study outcomes in the context of airway allergies.