Exercise training intervention represents an effective means to reduce adipose tissue mass, improve glycaemic control and increase whole-body oxygen uptake capacity (VO(2peak)) in obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and heart disease patients. In this manuscript, we review the impact of different exercise training modalities on clinical benefits of prolonged exercise intervention in these patient (sub)populations. By changing training modalities, significantly greater clinical benefits can be obtained. Greater training frequency and longer programme duration is associated with greater reduction in adipose tissue mass in obesity patients. A greater training frequency (up to 2 days/week) and a longer programme duration (up to 38 weeks) seems to be associated with greater improvements in VO(2peak) in heart disease patients. Longer programme duration and addition of resistance-type exercise further improve glycaemic control in T2DM patients. The first line of evidence seems to indicate that high-intensity interval exercise training has a greater impact on VO(2peak) in heart disease patients and insulin sensitivity in subjects with metabolic syndrome, but not on adipose tissue mass in obese subjects. However, it remains unclear whether addition of resistance-type exercise and continuous higher-intensity endurance-type exercise training are accompanied by greater improvements in VO(2peak) in heart disease patients. Furthermore, the impact of training session duration/volume on adipose tissue mass loss and glycaemic control in obesity and T2DM patients, respectively, is currently unknown. The impact of training frequency on glycaemic control remains to be investigated in T2DM patients.