Botulinum toxins are widely used worldwide for the treatment of medical and esthetic disorders. They are considered the gold standard for the treatment of muscular spasticity and facial dynamic wrinkles. Moreover, they are a valid alternative in the treatment of pain and hyperhidrosis. Several adverse events to their applications have been described, being the most frequent hematomas, migraines, palpebral ptosis, ectropion, or lack of response. Resistance to botulinum toxins in the medical field has been described, at higher dosages and short intervals. Nevertheless, resistance to botulinum toxin in esthetics has been considered traditionally anecdotic. Recent evidence suggests that resistance to botulinum toxins in esthetics may have higher prevalence than expected. A full analysis of the argument is given with up dated information regarding botulinum toxin resistance in medical and esthetic arenas; including elements for suspicion and diagnosis, valid alternatives for effective prevention, education and treatment of this misdiagnosed condition.