AbstractHistorically neglected, due to its biological peculiarities, the absence of a continuous long-term in vitro blood stage culture system and a propensity towards high morbidity rather than mortality,Plasmodium vivaxwas put back on the agenda during the last decade by the paradigm shift in the fight against malaria from malaria control to malaria eradication. While the incidence of the deadliest form of malaria,Plasmodium falciparummalaria, has declined since this paradigm shift took hold, the prospects of eradication are now threatened by the increase in the incidence of other human malaria parasite species.Plasmodium vivaxis geographically the most widely distributed human malaria parasite, characterized by millions of clinical cases every year and responsible for a massive economic burden. The urgent need to tackle the unique biological challenges posed by this parasite led to renewed efforts aimed at establishing a continuous, long-term in vitroP. vivaxblood stage culture. Based on recent discoveries on the role of nutrient sensing inPlasmodium’s pathophysiology, this review article critically assesses the extensive body of literature concerningPlasmodiumculture conditions with a specific focus on culture media used in attempts to culture differentPlasmodiumspp. Hereby, the effect of specific media components on the parasite’s in vitro fitness and the maturation of the parasite’s host cell, the reticulocyte, is analysed. Challenging the wide-held belief that it is sufficient to find the right parasite isolate and give it the right type of cells to invade forP. vivaxto grow in vitro, this review contends that a healthy side-by-side maturation of both the parasite and its host cell, the reticulocyte, is necessary in the adaptation ofP. vivaxto in vitro growth and argues that culture conditions and the media in particular play an essential role in this maturation process.