Mnemonics

"equal", "evaluate", "iterate"

Used alone

= assigns values as in common parlance
= after many infix operators creates a mutant assignment form of that operator
= inside a Signature marks parameters as optional and supplies default values
= after a property supplies it with an initial value
= at the beginning of a line may be introducing a POD element

Operators containing this character

:= aliases an identifier via runtime binding
::= aliases an identifier via compile time binding
=:= container identity comparitor
!= is short for !==
== compares for value equivalence
=== compares containers or values with dwimmery
>= <= and <=> are also comparisons. Note this means there is no assignment mutation.
=> "fat arrow" pair constructor
p5=> the perl5 compatibility fat arrow
= => = =>> <<= = <= = are feed operators

When used inside regexes

= is used to declare aliases and behaves a bit more like := in this usage.

Special Variables

As an adverb

Other Uses

Hyper operator and meta operator restrictions

Old, deprecated, or other language uses

=~ in Perl5 used to be for matching. That is ~~ in Perl6. =~ is always a syntax error in Perl6.
= as a prefix operator used to be used to do what is now Iterator.get (and IO.get, IO.lines)
=$*IN as prefix to filehandle is a case of the above which was common in early Perl6 documentation