The traditional view of the innate and the adaptive immune system has been adopted by researchers for decades: a dichotomy of a rapid, primitive, and non-specific (innate) immune response versus a slow, sophisticated, and specific (adaptive) immune response. Although very early studies (19th century, 1930s) showed that off-target immune protection was seen after specific immune challenges (e.g. BCG vaccine), nobody connected this with adaptability of the innate immune system. Recently, the laboratory of Netea and van der Meer challenged the classical dogma of innate and adaptive immune system and showed that the innate immune system holds the ability to be trained and ‘remember’ earlier challenges, as exemplified by more distinct immunological responses after secondary challenges (Cell Host & Microbe 2017). This has been termed ‘trained immunity’ and since 2011 when it was first proposed (Cell Host & Microbe 2011) seen a steep increase in PubMed hits. Although more studies should be performed to elucidate the underlying mechanisms, the concept of trained immunity holds great potential for improving the development of vaccines, trained immunity activators to treat sepsis-associated immune paralysis and trained immunity inhibitors/modulators for treatment of autoinflammatory diseases.