Restarting the tmux server every time you change the configuration is tedious and unnecessary.

From the shell:

tmux source-file ~/.tmux.conf

As a tmux command:

Prefix + :source-file ~/.tmux.conf

Just in case: the default prefix is CTRL + b

Those methods reload the tmux configuration without affection the sessions or windows.

Info: some changes still require a restart of the tmux server. If you were to remove a key bind, you would need to restart the tmux server or explicitly unbind the key.

The server stops running if all sessions are closed or you kill it with tmux kill-server or kill the process with pkill/kill. tmux kill-server will send a SIGTERM, where tmux kill-pane/kill-window/kill-session will send a SIGHUP.

Side note to the location of the configuration file:

Tmux looks in /etc/tmux.conf for a system-wide configuration file, and then for a configuration file in the current user's home directory, e.x. ~/.tmux.conf. If these files don't exist, tmux uses the default settings.