Sublingual immunotherapy (SLIT)-tablets represent a new allergen immunotherapy option for clinicians. In North America, there are five SLIT-tablets approved for the treatment of allergic rhinoconjunctivitis (ARC). No SLIT-drops products are currently approved in the United States or Canada. This work reviewed the efficacy of the timothy grass SLIT-tablet, five-grass SLIT-tablet, ragweed SLIT-tablet, house-dust mite SLIT-tablet, and tree SLIT-tablet in patients with ARC. All the SLIT-tablets showed consistent clinical efficacy for the treatment of ARC in large, double-blind, placebo-controlled trials, including for both patients who were monosensitized and those who were polysensitized. Treatment with house-dust mite SLIT-tablet has shown efficacy in patients who are pollen sensitized during their respective pollen seasons. In contrast to SLIT-tablets, efficacy studies of SLIT-drops show high heterogeneity of treatment effect. Although data are scarce, data that compared the efficacy of SLIT-tablets versus ARC pharmacotherapy generally indicated that SLIT-tablets had a greater benefit than pharmacotherapy when compared with placebo, particularly for perennial ARC. When compared with subcutaneous immunotherapy, analysis of these data indicated that SLIT-tablets had a benefit over subcutaneous immunotherapy in regard to safety but somewhat less benefit in regard to efficacy. The safety of SLIT-tablets has been well documented, and a U.S. Food and Drug Administration class label with safety considerations is present in the prescribing information for all SLIT-tablets. No new safety signals have been observed after reinitiating SLIT-tablets after a short treatment interruption.