Challenging behavior is highly prevalent in nursing home residents with dementia. For many of the residents, the challenging behavior was also the main reason of admission to the nursing home. The challenging behavior leads to loss of quality of life and stress and burden for caregivers, both informal and formal. Especially agitation and aggression are a challenge. Managing challenging behavior in residents with dementia asks for a systematic and multidisciplinary approach, focusing on finding and treating the underlying problems. Psychoactive drugs should be used on strict indication; psychosocial interventions are first-choice treatment. In this chapter, professionals are given guidance for a systematic, multidisciplinary, and timely detection, analysis, treatment, and evaluation of challenging behavior in nursing home residents with dementia.