At the end of their stint in Viet Nam, Col. John "Hannibal" Smith and his team were framed for robbing the Bank of Hanoi (which they had done, but under orders), and sent to a US military prison. They escaped and went on the run, pursued first by Col. Lynch and later by Col. Decker. While on the lam, they became heroes for hire, working as good-guy vigilantes around the US or the world. Hannibal was their leader and an expert at disguises. Face was the team's con artist and lady's man. BA (officially "Bad Attitude") was their mechanic, but also took care of mayhem and intimidation. The final member of the Team, "Howling Mad" Murdock, was an expert pilot, and a certified lunatic--they broke him out of a mental hospital whenever they needed him for a mission.

侦探小说家Richard Castle（内森·菲利安 Nathan Fillion 饰）因为一起连环杀人案结识了纽约警局的Kate Beckett（斯坦娜·卡蒂克 Stana Katic 饰），并对她产生了浓厚的兴趣。虽然Beckett强烈反对，Castle最终还是凭借 自己发达的人脉，在纽约警局“赖”了下来，跟在Beckett身后办案以寻找写作灵感。性格和背景迥异的两人在不断的斗嘴与摩擦中竟然渐渐培养出了默契，成了名符其实的最佳搭档。但Castle不顾Beckett的反对，私下调查Beckett母亲多年前的命案，一度导致两人的关系一度陷入僵局。当Richard那种 "随心所欲"、"自由散漫" 的作风与Beckett那种程序化的保守作风相抵触时，争论随之而来，火花也随之而来。是危险，还是浪漫？