The progress of information and communication technology has a positive impact, and it is a part of our everyday activities. In the same time, it presents an attack vector and vulnerability used by attackers to generate advanced cyber threats. Attackers use new and advanced tools to perform cyber-attacks, including AI-based malware, and in most of cases, they are ahead of the cyber defenders. The tools and attacks used by attackers require extensive time if analyzed manually and require significant automation so cyberspace can be effectively defended. As one of the best tools for the first line of defense is AI (Artificial intelligence)-based cyber defense mechanisms that can be used to react proactively (before the cyber-attack) or reactively (during the cyber-attack) in order to detect, restrict and stop the attack. This chapter gives a brief review of the usage of artificial intelligence as the first line of defense in cyberspace, using the model of defense in-depth, presenting AI-based tools and applications that already exist and are used for cyber defense.