Latin America made significant advances in control and elimination of malaria, particularly from 2000 to 2015, when symptomatic disease declined by 62% (from 1,181,095 cases in 2000 to 451,242 in 2015) and malaria-related deaths by 61.2% (from 410 to 159). Nonetheless, in 2016 a considerable increase in the number of cases (875,000) was reported in the region, with Venezuela making the largest single contribution (34.4%). Indeed, between 2000 and 2015, Venezuela witnessed an unprecedented 365% increase malaria cases followed by a 68% increase (319,765 cases) in late 2017. Here, Plasmodium vivax accounts for 71% of reported cases of malaria followed by P. falciparum (20%) and other Plasmodium infections (~ 9% of mixed and P. malariae cases). High malaria incidence is positively correlated with an increase in illegal mining activities in the south of the country. A complex pattern of limited, albeit persistent hot-spots of Plasmodium transmission is maintained principally by Anopheles darlingi Root, An. albitarsis Lynch s.l. and An. nuneztovari Gabaldon s.l. Clearing forests for mining activities creates favourable conditions for these vector species breeding. The increase in illegal mining activities is strongly linked to the Venezuelan socio-economic crisis. Highly mobile, often immunologically naïve, human populations migrate from different regions of the country to mining areas in search of economic opportunities. Many internal migrants may return to past-endemic malaria regions where viable mosquito populations exist, reintroducing malaria to areas where this infection had been previously eliminated. In addition, financial constraints generated by the current crisis have severely limited the procurement of malaria commodities, and hampered epidemiological surveillance, reporting activities,vector-control and disease-treatment efforts. All these factors have created ideal conditions for malaria epidemics and increases in morbidity and mortality. This re-emergence of malaria has set in place an epidemic of unprecedented proportions, not only in Venezuela but in the region. Indeed, Brazil has reported an escalating trend of imported cases from Venezuela rising from 1,538 (2014) to 3,129 (2017), representing 45% and 86% respectively, of the reported malaria cases in two main bordering municipalities of Brazil. The continued upsurge of malaria in Venezuela could soon become uncontrollable; jeopardizing the hard-won gains of the malaria control programme in Latin America. With 406,000 cases reported to WHO during 2017, Venezuela may now exhibit the largest malaria increase reported worldwide, thereby threatening Global Malaria Action Plan.