Today large software systems (i.e., giants) thrive in commodity markets, but are untrustworthy due to their numerous and inevitable software bugs that can be exploited by the adversary. Thus, the best hope of security is that some small, simple, and trustworthy software components (i.e., wimps) can be protected from attacks launched by adversary-controlled giants. However, wimps in isolation typically give up a variety of basic services (e.g., file system, networking, device I/O), trading usefulness and viability with security. Among these basic services, isolated I/O channels remained an unmet challenge over the past three decades. Isolated I/O is a critical security primitive for a myriad of applications (e.g., secure user interface, remote device control). With this primitive, isolated wimps can transfer I/O data to commodity peripheral devices and the data secrecy and authenticity are protected from the co-existing giants. This thesis addresses this challenge by proposing a new security architecture to provide services to isolated wimps. Instead of restructuring the giants or bloating the Trusted Computing Base that underpins wimp-giant isolation (dubbed underlying TCB), this thesis presents a unique on-demand I/O isolation model and a trusted add-on component called wimpy kernel to instantiate this model. In our model, the wimpy kernel dynamically takes control of the devices managed by a commodity OS, connects them to the isolated wimps, and relinquishes controls to the OS when done. This model creates ample opportunities for the wimpy kernel to outsource I/O subsystem functions to the untrusted OS and verify their results. The wimpy kernel further exports device drivers and I/O subsystem code to wimps and mediates the operations of the exported code. These two methodologies help to significantly reduce the size and complexity of the wimpy kernel for high security assurance. Using the popular and complex USB subsystem as a case study, this thesis illustrates the dramatic reduction of the wimpy kernel; i.e., over 99% of the Linux USB code base is removed. In addition, the wimpy kernel also composes with the underlying TCB, by retaining its code size, complexity and security properties.