SMTP is a TCP/IP protocol used in sending and receiving email. However, since it is limited in its ability to queue messages at the receiving end, it is usually used with one of two other protocols, POP3 or IMAP, that let the user save messages in a server mailbox and download them periodically from the server. In other words, users typically use a program that uses SMTP for sending e-mail and either POP3 or IMAP for receiving e-mail. On Unix-based systems, sendmail is the most widely-used SMTP server for e-mail. A commercial package, Sendmail, includes a POP3 server. Microsoft Exchange includes an SMTP server and can also be set up to include POP3 support.

SMTP usually is implemented to operate over Internet port 25. An alternative to SMTP that is widely used in Europe is X.400. Many mail servers now support Extended Simple Mail Transfer Protocol (ESMTP), which allows multimedia files to be delivered as e-mail.