Sarcoidosis can be a major therapeutic challenge given its multiplicity of clinical presentations, variable combination of organ involvement and severity, and unpredictable longitudinal behaviour. Six manifestations of sarcoidosis are especially difficult to manage because of (i) an incomplete knowledge of causation – fatigue and small fibre neuropathy, (ii) the rare occurrence in sarcoidosis – intra-abdominal complications or (iii) the potentially life-threatening consequences in some patients – neurological disease, pulmonary hypertension and hypercalcaemia. In none of these situations have a prospective, double-blind, placebo-controlled trial of any therapy been conducted. Despite this absence of any firm evidence base to support therapeutic recommendations, these six entities can be extremely problematic for the practising clinician. It is for this reason that we have focused in this review on these six disease manifestations and provided a synopsis of each problem together with suggested treatment approaches, based on an analysis of the current literature.