故事主要讲述了几世前一位默默无名的小药童,不愿与无良药商同流合污,用生命守护药草,最终药草吸附了药童的鲜血有了灵性。几世轮回,以钩藤为首的四味药草(钩藤、曼罗、水苏、豆蔻)幻化为药灵,有了人的模样,他们必须再次寻找到一位真心驭药人,用鲜血滋养药身,才能真正修炼成仙。而一旦他们成仙,世间也便再无这味药草。云来镇小药师林东笙,心怀济世之梦,努力寻找这四味绝迹药草治病救人。在双方互相寻找的过程中,曼罗等终于发现林东笙即前世用命守护自己的种药小子,想要报恩时,却被与林家世代结仇的刘虎设下诡计,陷害林东笙蓄意下毒,引来官府及药灵谷的双重追杀。曼罗为保护林东笙不惜与钩藤、水苏等决裂,在拯救苍生与自我获益之间,每个人都面临着重要抉择……
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