Migraine is a common disease which causes significant burden to individuals, in terms of personal suffering and activity reduction, and to societies, in terms of disease cost. The purpose of this study is to identify the most relevant psychosocial difficulties related to migraine, the variables associated with them and the most relevant determinants of their evolution over time. MEDLINE and PsychINFO were searched for studies published in English between 2000 and 2010 that examined psychosocial difficulties in persons with migraine with and without aura, from clinical trials and observational studies. Information on the description of each difficulty, its determinants of onset and change over time and associated variables were extracted and categorized at a higher level. In total, 34 difficulties have been collected from 51 papers: the most frequent were reduced vitality and fatigue, emotional problems, pain, difficulties at work, general physical and mental health, social functioning and global disability. Evidence exists that pharmacological treatments have an impact toward improvement in patients' difficulties, in particular emotional problems, physical and mental health, difficulties with employment and global disability. Migraine treatments and decreased headaches frequency are the major determinants of improvements in psychosocial difficulties, while no information is available for determinants of worsening; understanding the role of such factors is of primary public health relevance, given the high prevalence and the relevant personal and societal costs of migraine.