The upper motor neuron (UMN) syndrome is a collection of interactive positive signs (associated with spastic hypertonia) and negative signs, such as muscle weakness and loss of voluntary control. In clinical practice, the distinction between active and passive functions allows identifying appropriate treatment objectives. During the last decades, many studies have evaluated the possibility to treat UMN syndromes with botulinum neurotoxin (BoNT). They have shown that BoNT is effective in controlling upper limb spasticity in adults. The clinical improvement is more consistent in the distal joints and the reduction of muscle hypertonia is dose-dependent. The functional efficacy of BoNT for lower limb spasticity has not been documented as well, as some series report efficacy in reducing muscle tone in the lower limb, but not in improving walking. The functional benefit arising from the reduction of spasticity is often difficult to judge in the context of the complex phenomenology of the UMN syndrome. Certain data indicate that some disabilities related to passive and active function in the upper limb can improve with treatment. However, to date, the functional improvement after BoNT treatment in patients with UMN symptoms remains a point of ambiguity in the literature. BoNT is overall well tolerated and must be regarded as a safe treatment intervention. Safety data are abundant in the literature for type-A toxin and scant for type-B toxin. There is no clear evidence to suggest the best time to introduce BoNT injections in the management of UMN syndromes. A common sense approach would be to introduce BoNT treatment as early as possible, in order to prevent further complications including contractures.