The increasing distribution and prevalence of fasciolosis in both human and livestock are concerning. Here, we examine the various types of factors influencing fasciolosis transmission and burden and the interrelations that may exist between them. We present the arsenal of molecules, 'adjusting' capabilities and parasitic strategies of Fasciola to infect. Such features define the high adaptability of Fasciola species for parasitism that facilitate their transmission. We discuss current environmental perturbations (increase of livestock and land use, climate change, introduction of alien species and biodiversity loss) in relation to fasciolosis dynamics. As Fasciola infection is directly and ultimately linked to livestock management, living conditions and cultural habits, which are also changing under the pressure of globalization and climate change, the social component of transmission is also discussed. Lastly, we examine the implication of increasing scientific and political awareness in highlighting the current circulation of fasciolosis and boosting epidemiological surveys and novel diagnostic techniques. From a joint perspective, it becomes clear that factors weight differently at each place and moment, depending on the biological, environmental, social and political interrelating contexts. Therefore, the analyses of a disease as complex as fasciolosis should be as integrative as possible to dissect the realities featuring each epidemiological scenario. Such a comprehensive appraisal is presented in this review and constitutes its main asset to serve as a fresh integrative understanding of fasciolosis.