In applications design, TLS is usually implemented on top of any of the Transport Layer protocols, encapsulating the application-specific protocols such as HTTP,FTP, SMTP, NNTP and XMPP. Historically it has been used primarily with reliable transport protocols such as the Transmission Control Protocol (TCP). However, it has also been implemented with datagram-oriented transport protocols, such as the User Datagram Protocol (UDP) and the Datagram Congestion Control Protocol(DCCP), usage which has been standardized independently using the term Datagram Transport Layer Security (DTLS).

A prominent use of TLS is for securing World Wide Web traffic carried by HTTP to form HTTPS. Notable applications are electronic commerce and asset management. Increasingly, the Simple Mail Transfer Protocol (SMTP) is also protected by TLS . These applications use public key certificates to verify the identity of endpoints.

TLS can also be used to tunnel an entire network stack to create a VPN, as is the case with OpenVPN. Many vendors now marry TLS's encryption and authentication capabilities with authorization. There has also been substantial development since the late 1990s in creating client technology outside of the browser to enable support for client/server applications. When compared against traditional IPsec VPN technologies, TLS has some inherent advantages in firewall and NATtraversal that make it easier to administer for large remote-access populations.

TLS is also a standard method to protect Session Initiation Protocol (SIP) application signalling. TLS can be used to provide authentication and encryption of the SIP signalling associated with VoIP and other SIP-based applications.