The challenge to the modern system of international security and stability is crimes against humanity, which threaten democratic processes, violate international principles and make peaceful coexistence in a globalized society impossible. The conceptual foundations and theoretical and methodological approaches to the definition of crimes against humanity have been studied. The most optimal definition is presented in the Rome Statute, where crimes against humanity are interpreted as crimes against peace, stability and security, as inhuman acts committed against the civilian population. Considerable attention in the study is paid to the analysis of approaches to the classification of crimes against humanity. In particular, such types as: murder; extermination; enslavement; deportation; persecution; the crime of apartheid; imprisonment; torture; rape; sexual slavery, forms of sexual violence; forced disappearance of persons, etc. have been described. The intensification of crimes against humanity and their intensive growth force the international community to consolidate its efforts to combat them. In the article, the institutional and legal mechanisms of counteraction to crimes against humanity have been studied; international political, socio-economic sanctions and preventive security measures have been identified. It has been emphasized that the international community developed new principles of international cooperation in combating crimes against humanity; flexible conditions for the implementation of humanitarian missions and actions have been created; effective and efficient methods and forms of counteraction to crimes against humanity have been developed. In the article, the activities of international governmental and non-governmental organizations in combating illegal actions have been studied; their decisive role in preventing and countering crimes against humanity has been substantiated. It is worth noting the activities of the League of Nations, the UN, OSCE, NATO, EU, and regional organizations: the African Union, the Economic Community of West African States (ECOWAS), the Association of Southeast Asian Nations (ASEAN). International non-governmental organizations also play an important role in combating crimes against humanity. In particular, there are the International Committee of the Red Cross and influential human rights non-governmental organizations such as Amnesty International, Human Rights Watch, the International Commission of Jurists, the International Federation for Human Rights, TRIAL International, Reporters without Borders, Interpol, Europol, etc. An important element in the effectiveness of combating crimes against humanity is a stable international cooperation, active consolidated cooperation between states and their desire for a constructive dialogue.