We aimed to report an update of the systematic review by Petrén et al. (2003). The objective was to evaluate how orthodontic treatments can affect unilateral posterior crossbite (UPXB) in primary and early mixed dentition. Several databases were consulted, and articles published between January 2002 and March 2020 were selected. This review examines the following studies: randomized clinical trials, prospective and retrospective studies with concurrent untreated or normal control groups, and clinical trials comparing at least two treatment strategies. Among the 1581 articles retrieved from the searches, 11 studies were included. Quad-helix (QH) and expansion plate (EP) appliances were compared in three studies. One study compared rapid maxillary expansion (RME) treatment anchored on primary dentition otherwise on permanent molars. One study compared RME and a modified RME with arms extended until deciduous canine and EP. Four studies evaluated the effects of expansion appliances compared with a control group. Compared with the previous review, the quality of the included studies is higher. However, heterogeneity of treatments, different strategies in measurements, lack of a similar follow-up length, and absence of a cost-effectiveness analysis preclude the possibility of providing reliable scientific evidence on the most effective UPXB treatment in primary and early mixed dentition.