Hypertension is a major health concern, and current recommendations for blood pressure management (lifestyle modifications and pharmacological intervention) have not been universally successful. For two decades, isometric exercise training (IET) has become established as effective at reducing in resting BP (RBP) in a short period (4–10 weeks). The most common IET modes have comprised isometric handgrip (IHG) or isometric bilateral leg (IBL) training and 4 × 2-min contractions at ∼20–50% maximal voluntary contraction with 1–5-min rest between. Although this type of exercise training could have important implications, for hypertensive patients and in preventing hypertension development, little is known about the mechanisms responsible for IET-induced RBP reductions. This uncertainty derives from a lack of understanding concerning the most effective IET programs for specific populations. Possible influential factors and mechanisms include age, sex, pre-existing disease and medication, and IET-induced adaptations in the exercising muscle and nervous system, which are discussed in this review. Designing effective IET programs may involve manipulation of exercise intensity, frequency, duration and mode, as well as consideration of yet discovered mechanisms for RBP reductions. We call for additional research designed to understand more about the mechanisms involved in IET-induced RBP reductions for maximum effectiveness.